Fanconi anemia (FA) is a cancer susceptibility syndrome associated with developmental abnormalities and bone marrow failure. Because of the unique cellular hypersensitivity to DNA crosslinking agents FA is considered to be a DNA repair disorder. The first (of at least eight) of the known FA complementation group genes, FANCC, was cloned more than seven years ago. Despite substantial efforts to discover the function of the FANCC protein, and functions of the proteins encoded by the other more recently cloned FA genes (FANCA and FANCG), the basic defect is still unknown. We used a yeast two hybrid screen to identify a new POZ-zinc finger protein (termed FAZF) which interacts with FANCC. We recently showed that FAZF is a transcriptional repressor similar to the promyelocytic zinc finger protein (PLZF). PLZF represses transcription of target genes by recruitment of histone deacetylase through the SMRT-mSin3-HDAC co-repressor complex and tethering the complex to specific DNA target sequences. The FANCC/FAZF interaction is intriguing because it suggests that the FANCC protein may be interacting with components of the histone deacetylase complex. We propose to investigate FAZF and its relationship to FA by: (1) Analyzing FAZF/FANCC interaction in response to DNA damage, determine if FAZF is an FA complementing protein, compare the expression of FAZF and FANCC in primary hematopoietic cells (2) Analyze the consequences of enforced expression of FAZF, identify FAZF's binding partners, determine if FAZF is phosphorylated in response to DNA damage (3) Produce and examine the phenotype of FAZF nullizygous mice.